Neuroprotective role of sialic-acid-binding immunoglobulin-like lectin-11 in humanized transgenic mice.

Brain aging is a chronic process linked to inflammation, microglial activation, and oxidative damage, which can ultimately lead to neuronal loss. Sialic acid-binding immunoglobulin-like lectin-11 (SIGLEC-11) is a human lineage-specific microglial cell surface receptor that recognizes -2-8-linked oligo-/polysialylated glycomolecules with inhibitory effects on the microglial inflammatory pathways. Recently, the gene locus was prioritized as a top tier microglial gene with potential causality to Alzheimer's disease, although its role in inflammation and neurodegeneration remains poorly understood.

Transcriptional profile of infection in people living with HIV.

In people with HIV-1 (PWH), (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals.

The small hive beetle's capacity to disperse over long distances by flight.

The spread of invasive species often follows a jump-dispersal pattern. While jumps are typically fostered by humans, local dispersal can occur due to the specific traits of a species, which are often poorly understood. This holds true for small hive beetles (Aethina tumida), which are parasites of social bee colonies native to sub-Saharan Africa.

Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.

Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.

Design, Setting, And Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age.

A Rab-bit hole: Rab40 GTPases as new regulators of the actin cytoskeleton and cell migration.

The regulation of machinery involved in cell migration is vital to the maintenance of proper organism function. When migration is dysregulated, a variety of phenotypes ranging from developmental disorders to cancer metastasis can occur. One of the primary structures involved in cell migration is the actin cytoskeleton.

Timing of Complete Revascularization with Multivessel PCI for Myocardial Infarction.

Background: In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of nonculprit lesions should be performed remains unknown.

Methods: We performed an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion followed by staged multivessel PCI of nonculprit lesions within 19 to 45 days after the index procedure (staged group).

Dectin-1 multimerization and signaling depends on fungal β-glucan structure and exposure.

Dectin-1A is a C-type lectin innate immunoreceptor that recognizes β-(1,3;1,6)-glucan, a structural component of Candida species cell walls. β-Glucans can adopt solution structures ranging from random coil to insoluble fiber due to tertiary (helical) and quaternary structure. Fungal β-glucans of medium and high molecular weight are highly structured, but low molecular weight glucan is much less structured.

Accumulation of TMEM106B C-terminal fragments in neurodegenerative disease and aging.

Several studies using cryogenic electron microscopy (cryo-EM) techniques recently reported the isolation and characterization of novel protein filaments, composed of a C-terminal fragment (CTF) of the endolysosomal transmembrane protein 106B (TMEM106B), from human post-mortem brain tissue with various neurodegenerative conditions and normal aging. Genetic variation in TMEM106B is known to influence the risk and presentation of several neurodegenerative diseases, especially frontotemporal dementia (FTD) caused by mutations in the progranulin gene (GRN). To further elucidate the significance of TMEM106B CTF, we performed immunohistochemistry with antibodies directed against epitopes within the filament-forming C-terminal region of TMEM106B.

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.

Background And Objectives: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).

Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice.

The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined.

Mesoionic Dithiolates (MIDts) Derived from 1,3-Imidazole-Based Anionic Dicarbenes (ADCs).

Mesoionic dithiolates [(MIDt )Li(LiBr) (THF) ] (MIDt ={SC(NDipp)} CAr; Dipp=2,6-iPr C H ; Ar=Ph 3 a, 3-MeC H (3-Tol) 3 b, 4-Me NC H (DMP) 3 c) and [(MIDt )Li(THF) ] (4) are readily accessible (in≥90 % yields) as crystalline solids on treatments of anionic dicarbenes Li(ADC ) (2 a-c) (ADC ={C(NDipp) } CAr) with elemental sulfur. 3 a-c and 4 are monoanionic ditopic ligands with both the sulfur atoms formally negatively charged, while the 1,3-imidazole unit bears a formal positive charge. Treatment of 4 with (L)GeCl (L=1,4-dioxane) affords the germylene (MIDt )GeCl (5) featuring a three-coordinated Ge atom.

Cardiac Effects of Novel Histamine H Receptor Agonists.

In an integrative approach, we studied cardiac effects of recently published novel H receptor agonists in the heart of mice that overexpress the human H receptor (H-TG mice) and littermate wild type (WT) control mice and in isolated electrically driven muscle preparations from patients undergoing cardiac surgery. Under our experimental conditions, the H receptor agonists UR-Po563, UR-MB-158, and UR-MB-159 increased force of contraction in left atrium from H-TG mice with pEC values of 8.27, 9.

Charcot-Marie-tooth disease causing mutation (p.R158H) in pyruvate dehydrogenase kinase 3 (PDK3) affects synaptic transmission, ATP production and causes neurodegeneration in a CMTX6 C. elegans model.

Charcot-Marie-Tooth (CMT) is a commonly inherited, non-fatal neurodegenerative disorder that affects sensory and motor neurons in patients. More than 90 genes are known to cause axonal and demyelinating forms of CMT. The p.

Prognostic Assessment in High-Grade Soft-Tissue Sarcoma Patients: A Comparison of Semantic Image Analysis and Radiomics.

Background: In patients with soft-tissue sarcomas of the extremities, the treatment decision is currently regularly based on tumor grading and size. The imaging-based analysis may pose an alternative way to stratify patients' risk. In this work, we compared the value of MRI-based radiomics with expert-derived semantic imaging features for the prediction of overall survival (OS).

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Nickel-Catalyzed Intramolecular 1,2-Aryl Migration of Mesoionic Carbenes (iMICs).

Intramolecular 1,2-Dipp migration of seven mesoionic carbenes (iMIC ) 2 a-g (iMIC =ArC{N(Dipp)} CHC; Ar=aryl; Dipp=2,6-iPr C H ) under nickel catalysis to give 1,3-imidazoles (IMD ) 3 a-g (IMD =ArC{N(Dipp)CHC(Dipp)N}) has been reported. The formation of 3 indicates the cleavage of an N-C bond and the subsequent formation of a C-C bond in 2, which is unprecedented in NHC chemistry. The use of 3 in accessing super-iMICs (5) (S-iMIC=ArC{N(Dipp)N(Me)C(Dipp)}C) has been shown with selenium (6), gold (7), and palladium (8) compounds.

A non-helical region in transmembrane helix 6 of hydrophobic amino acid transporter MhsT mediates substrate recognition.

MhsT of Bacillus halodurans is a transporter of hydrophobic amino acids and a homologue of the eukaryotic SLC6 family of Na -dependent symporters for amino acids, neurotransmitters, osmolytes, or creatine. The broad range of transported amino acids by MhsT prompted the investigation of the substrate recognition mechanism. Here, we report six new substrate-bound structures of MhsT, which, in conjunction with functional studies, reveal how the flexibility of a Gly-Met-Gly (GMG) motif in the unwound region of transmembrane segment 6 (TM6) is central for the recognition of substrates of different size by tailoring the binding site shape and volume.

Antibody against TDP-43 phosphorylated at serine 375 suggests conformational differences of TDP-43 aggregates among FTLD-TDP subtypes.

Aggregation of hyperphosphorylated TDP-43 is the hallmark pathological feature of the most common molecular form of frontotemporal lobar degeneration (FTLD-TDP) and in the vast majority of cases with amyotrophic lateral sclerosis (ALS-TDP). However, most of the specific phosphorylation sites remain to be determined, and their relevance regarding pathogenicity and clinical and pathological phenotypic diversity in FTLD-TDP and ALS-TDP remains to be identified. Here, we generated a novel antibody raised against TDP-43 phosphorylated at serine 375 (pTDP-43) located in the low-complexity domain, and used it to investigate the presence of S375 phosphorylation in a series (n = 44) of FTLD-TDP and ALS-TDP cases.

Methodology for the American Society of Hematology VTE guidelines: current best practice, innovations, and experiences.

Background: Methods for the development of clinical guidelines have advanced dramatically over the past 2 decades to strive for trustworthiness, transparency, user-friendliness, and rigor. The American Society of Hematology (ASH) guidelines on venous thromboembolism (VTE) have followed these advances, together with application of methodological innovations.

Objective: In this article, we describe methods and methodological innovations as a model to inform future guideline enterprises by ASH and others to achieve guideline standards.

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

Background: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19).

Purpose: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19.

Data Sources: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020.

A user guide to the American Society of Hematology clinical practice guidelines.

Since November 2018, Blood Advances has published American Society of Hematology (ASH) clinical practice guidelines on venous thromboembolism, immune thrombocytopenia, and sickle cell disease. More ASH guidelines on these and other topics are forthcoming. These guidelines have been developed using consistent processes, methods, terminology, and presentation formats.

Isolation of singlet carbene derived 2-arsa-1,3-butadiene radical cations and dications.

2-Arsa-1,3-butadienes (L)As(cAACR) (L = PhC[double bond, length as m-dash]C{(NDipp)CH}2, Dipp = 2,6-iPr2C6H3; cAACR = C{(NDipp)CMe2CH2C(R)}, R = Me22a, R = cyclohexyl (Cy) 2b) and the corresponding radical cations [(L)As(cAACR)]GaCl4 (R = Me23a, Cy 3b) and dications [(L)As(cAACR)](GaCl4)2 (R = Me 4a, Cy 4b) featuring a C[double bond, length as m-dash]C-As[double bond, length as m-dash]C π-conjugated framework are reported.

Isolation of singlet carbene derived 2-phospha-1,3-butadienes and their sequential one-electron oxidation to radical cations and dications.

A synthetic strategy for the 2-phospha-1,3-butadiene derivatives [{(IPr)C(Ph)}P(cAAC)] () and [{(IPr)C(Ph)}P(cAAC)] () (IPr = C{(NDipp)CH}, Dipp = 2,6-iPrCH; cAAC = C{(NDipp)CMeCHCMe}; cAAC = C{(NDipp)CMeCHC(Cy)}, Cy = cyclohexyl) containing a C[double bond, length as m-dash]C-P[double bond, length as m-dash]C framework has been established. Compounds and have a remarkably small HOMO-LUMO energy gap (: 5.09; : 5.

Towards Covalent Photosensitizer-Polyoxometalate Dyads-Bipyridyl-Functionalized Polyoxometalates and Their Transition Metal Complexes.

A triol-functionalized 2,2'-bipyridine (bpy) derivative has been synthesized and used for the tris-alkoxylation of polyoxometalate (POM) precursors. The resultant POM-bpy conjugates of the Wells-Dawson- and Anderson-type feature a C-C bond as a linkage between the POM and bpy fragments. This structural motif is expected to increase the hydrolytic stability of the compounds.

Application of High-Sensitivity Troponin in Suspected Myocardial Infarction.

Background: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes.

Methods: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design.